Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: a meta-analysis of randomized controlled trials

Zhao YT, Chen Q, Sun YX, Li XB, Zhang P, Xu Y, Guo JH

CRD summary

This review concluded that omega-3 fatty acids dietary supplements given to people with coronary heart disease reduced the incidence of sudden death in people with myocardial infarction, but may have had an adverse effect on people with angina. Some methods of the review were not well described and these conclusions may need to be treated with caution.

Authors' objectives

To assess the effects of dietary or supplementary intake of omega-3 fatty acids on sudden cardiac death, cardiac death and all-cause mortality.

Searching

PubMed, EMBASE and The Cochrane Library were searched from 1966 to June 2007. Search terms were reported. Bibliographies of identified studies and reviews were checked.

Study selection

Randomised controlled trials (RCTs) for the secondary prevention of coronary heart disease that compared dietary or non-dietary omega-3 fatty acids to control diet or placebo, had a follow-up of six months or longer and that reported on sudden cardiac death (SCD) were sought. Studies on people with implantable cardioverter defibrillators were excluded.

Participants in the included studies were post myocardial infarction, with coronary heart disease (CHD), had stable angina or suspected myocardial infarction or percutaneous transluminal coronary angioplasty. The proportion of men ranged from 31% to 100%; most studies included more men than women. Mean ages ranged from 48 to 63 years. Some studies only included participants who had myocardial infarction; in others between 0 and 90% had a history of myocardial infarction. Treatment consisted of alpha-linolenic acid, eicosapentaenoic acid (EPA), EPA plus statin, omega-3 fatty acid, docosahexaenoic acid (DHA), linolenic acid, oily fish or fish oil. Controls were dietary advice, aluminium hydroxide, corn oil, diet, fruit vegetables and oats, statin or no intervention. Where reported, between 8% and 63% additionally took beta-blockers. Excluding the study where statin was part of the treatment and control plan, between 5% and 17% took statins. Mean follow-up ranged from six to 108 months.

Two authors independently assessed studies for inclusion. Disagreement was resolved by consensus.

Assessment of study quality

The quality of studies was assessed using the Jadad score (award of up to 5 points for the criteria of randomisation, blinding and treatment of withdrawals and dropouts).

Where studies had more than one treatment (or control) group, results for these were combined during the analysis. Relative risk (RR) and 95% confidence intervals (CI) were calculated for each outcome.

The authors did not state how many reviewers performed the data extraction.

Methods of synthesis

As heterogeneity was present, pooled relative risks with 95% CI were calculated using a random-effects model. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were used to investigate the effects of clinical heterogeneity (<50% versus >80% with myocardial infarction at baseline) and type of omega-3 used (dietary versus supplementary omega-3). Sensitivity analysis was carried out removing smaller studies (<1,000 participants). Publication bias was not assessed because of the small number of studies.

Results of the review

Eight RCTs (20,997 participants) were included. One trial contributed more than half of the participants (11,323 participants). Two studies scored 5, four scored 3 and two scored 2 for quality on the Jadad scale.

Omega-3 fatty acids had no effect on sudden cardiac death (RR 0.71, 95% CI 0.43 to 1.18) or all-cause mortality (RR 0.77, 95% CI 0.58 to 1.01); there was some reduction in cardiac death (RR 0.71, 95% CI 0.50 to 1.00).

Subgroup analyses: In those who were at higher risk (>80% with myocardial infarction; four trials), sudden death (RR 0.43, 95% CI 0.20 to 0.91), cardiac death (RR 0.57, 95% CI 0.37 to 0.88) and all-cause mortality (RR 0.66, 95% CI 0.47 to 0.93) were all reduced with omega-3. Heterogeneity was present for these analyses, but this was removed or reduced by exclusion of one trial with no effect on the results. Omega-3 had no effect in the low risk group (<50% with myocardial infarction; four trials).

Sudden death was reduced in those studies where omega-3s were given as supplements (RR 0.72, 95% CI 0.58 to 0.91; five trials), but not in those where diet or dietary advice was used (three trials).

A sensitivity analysis that excluded smaller studies and one study considered to have methodological problems produced similar results to the main analysis.

Authors' conclusions

Omega-3 fatty acids given as dietary supplements reduced incidence of sudden death in people with myocardial infarction, but may have had adverse effects on people with angina.

CRD commentary

The aims of this review were clearly stated in terms of inclusion criteria, study design and outcomes. The search covered a number of relevant sources. There was no mention of whether studies in any language and unpublished studies were eligible for inclusion, so studies could have been missed. The authors were unable to assess for possible publication bias. It was unclear whether publication and language biases may have affected the results of the review. The methods of study selection and quality assessment were likely to have reduced the possibility of reviewer error or bias. There was no mention of how data were extracted and so it was not possible to comment on this. The quality of included studies was assessed, although scales are not considered to be the most reliable way of doing this. Data were pooled appropriately and heterogeneity was investigated. In view of these comments, caution may be required in interpreting the conclusions.

Implications of the review for practice and research

Practice: The authors stated that evidence supported use of omega-3 fatty acids for prevention of sudden death in people with prior myocardial infarction, but not in people with angina.

Research: The authors stated that further research was needed to assess the impact of omega-3 fatty acids on people with coronary heart disease and to investigate possible mechanisms for reduction of sudden death.

Funding

Major State Basic Research Development Program of China (2007CB512008).

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.